v-xEPA United States Environmental Protection Agency Health Effects Research Laboratory Research Triangle Park NC 27711 Research and Development EPA-600/S1-81-066 Dec. 1981 Project Summary Studies in Children Exposed to Low Levels of Lead Herbert L. Needleman Two separate studies were con- ducted with the overall objective of examining the impact of lead at low dose on the neuropsychological func- tion of children. In the first study, a sample of children identified as having elevated lead levels in the dentine of shed deciduous teeth (N = 19) were compared to chil- dren with low dentine lead (N = 22) on electroencephalograms and a panel of 8 auditory and speech processing tasks. Quantitative electroencephalograms were obtained from 20 sites under 4 conditions in these subjects. The spectrum from 0.5 - 32 Hz was ex- amined; four bands were studied (alpha, beta, delta, and theta) under four conditions. Of the 320 compari- sons, 10 differed at P - 0.025 or less (Wilcoxin-Mann, Whitney two sample test). These 10 features, nine behav- ioral measures previously obtained, and maternal I.Q. were then submitted to multivariate analysis. A stepwise linear discriminant function analysis showed that adding the EEG to behav- ioral analysis in the model increased the discriminating power from P = 0.015 to P = 0.001. The most useful diagnostic features were EEG slowing (delta) over the parietal cortex and decreased full scale I.Q. Of the 8 speech and auditory out- comes studied, significant differences favoring the low lead group were found on three measures of auditory processing: (1) Goldman-Fristoe- Woodcock Auditory Selective Atten- tion Test, (2) Staggered Spondaic Word Test (Left noncompeting), (3) Speech Discrimination. This Project Summary was devel- oped by EPA's Health Effects Research Laboratory, Research Triangle Park, NC, to announce key findings of the research project that is fully docu- mented in a separate report of the same title (see Project Report ordering information at back). Introduction While the toxicity of lead at high dose is widely acknowledged, considerable controversy exists as to whether lesser doses produce adverse health effects. Lead is known to inhibit certain enzyme systems at extremely low concentra- tions. Among those most sensitive are D-aminolevulinic acid dehydrase, adenyl cyclase, and ferrochelatase. It is not, however, universally accepted that these biochemical changes and other changes represent adverse health ef- fects. For the purposes of the investigations described below, an adverse health effect is defined as "an alteration in the functioning of an organism which di- minishes its ability to adapt to a chang- ing environment. As a result, the orga- nism's longevity, vigor, or reproductive capacity is reduced." In a changing environment, the ability to register change and then make decisions based upon the data is essential to survival. The organ in which these executive ------- functions primarily reside is the central nervous system. The organizing princi- ple of these investigations is that the child's CNS is a candidate site for the early expression of adverse effects of lead exposure. The Lead Exposure ' Program at Children's Hospital Medical Center has focused on CNS performance. Earlier studies by the group had reported that children thought to be undamaged by lead, but who had elevated dentine levels, were less able on a number of measures of CNS function when com- pared to controls. Among the perform- ances which appeared sensitive to lead were verbal intelligence, auditory and speech processing, attention and class- room behavior. This study examines the electrophysi- ology of the CNS of a subsample of high and low lead subjects, and also compares them on a number of other measures of auditory and speech processing. A separate sample of children from an- other city were evaluated by teacher ratings, family history, and their dentine lead levels measured. This offered an opportunity, not only to replicate our previous observations, but to evaluate the effects of lead on classroom per- formance while controlling more com- pletely for other covariates which could be confounding. Conclusions Study I Alterations in neuropsychologicfunc- tion were demonstrated in electroen- cephalograms of asymptomatic children with elevated body lead burdens. These changes tended to be located in midline brain structures. The addition of EEC analysis to a battery of psychologic outcomes sharpened diagnostic pre- cision remarkably. Statistically significant decrease in function was found on three of nineteen speech processing outcomes. Outcomes tended to favor low lead subjects gen- erally. The relatively small sample size may be responsible for the failure of certain outcomes to reach statistical significance. Study II Teachers' Behavioral Ratings as a Function of Lead Burden. The proportion of negative teachers' 1 reports of classroom behavior tended to increase with increasing dentine lead concentrations. The items most sensitive to lead were distractibility, disorganiza- tion, ability to follow a sequence of directions, and overall classroom func- tioning. After data reduction by cluster analy- sis, the cluster containing the items "distractible" and "disorganized" was found most sensitive to lead exposure. The impact of lead was evaluated by stepwise multiple logistic regression. A significant (p = 0.013) lead effect was found, controlling for major covariates. This study replicated in part a previous investigation from this laboratory which shows that teachers' assessments of classroom behavior are sensitive to lead exposure. It goes further than that study by controlling for a number of covariates that could be related to outcome. The ability o'f the child to inhibit irrelevant stimuli is critical to the task of academic learning. The item "distractible" which evaluates that ability is consistently sensitive to lead exposure. It is reason- able to expect that this deficit is related to the impaired performance on speech processing measured here. Recommendations These studies add to the weight of those which report lead effects at low dose, and demonstrate that the threshold for appearance of adverse behavioral effects is a function of the sensitivity of the methods brought to bear on measur- ing outcome. The findings of alterations in EEC, speech processing, and classroom be- havior in samples clinically assumed to be free of frank toxicity supports the prudence and hygienic utility of reducing lead in the environment available to children. Studies of lead effects in children, should attend to those behaviors which are expressions o'f the organism'sability to focus attention. ------- Herbert L. Needleman, formerly with Children's Hospital Medical Center, Boston, MA, is now with the University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15261. Carl Hayes is the EPA Project Officer (see below). The complete report, entitled "Studies in Children Exposed to Low Levels of Lead," (Order No. PB 82-108 432; Cost: $8.00, subject to change) will be available only from: National Technical Information Service 5285 Port Royal Road Springfield, VA 22161 Telephone: 703-487-4650 The EPA Project Officer can be contacted at: Health Effects Research Laboratory U. S. Environmental Protection Agency Research Triangle Park, NC 27711 ff U S GOVERNMENT PRINTING OFFICE, 1981 — 599-017/7409 ------- United States Environmental Protection Agency Center for Environmental Research Information Cincinnati OH 45268 Postage and Fees Paid Environmental Protection Agency EPA 335 Official Business Penalty for Private Use $300 ii i> fi'MVlK KtUlUN 5 ?30 S U CHICAGO II PRUTHCI ------- |